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Immune Cell Infiltration and the Expression of PD-1 and PD-L1 in Primary PDGFRA-Mutant Gastrointestinal Stromal Tumors

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Purpose

To characterize the immune cell profile and expression of PD-1, PD-L1, and IDO in PDGFRA-mutant gastrointestinal stromal tumors (GISTs).

Methods

The clinicopathological data of PDGFRA-mutant GIST patients who received surgical resection in Zhongshan Hospital between January 2013 and August 2019 were reviewed retrospectively. The specimens of tissue chips were detected for immune cell infiltration and the expression of PD-1, PD-L1, and IDO by immunohistochemical staining.

Results

CD3+, CD8+, and CD68+ cells were the main infiltrating immune cells in the 42 patients included in this study. In addition, CD4+, CD56+, Foxp3+, and CD20+ cells were also observed. A higher CD8+ T cell count was associated with smaller tumor size and PDGFRA D842V mutation (P = 0.047, P = 0.005). A higher CD3+ and CD68+ cell count was associated with a higher mitotic index (P = 0.022, P = 0.006). CD4+ and CD20+ cell count was associated with tumor morphology (P = 0.002, P = 0.045). PD-1 expression was present in 37 (88%) samples. Eighteen samples were positive for PD-L1 expression, and it was higher in small vs. large tumors (P = 0.012) and epithelioid and mixed cell type vs. spindle cell type GISTs (P = 0.046). IDO expression was positive in all 42 patients. The number of CD4+ cells was significantly greater in the specimens with high IDO expression (P = 0.012).

Conclusion

There were abundant infiltrating immune cells in PDGFRA-mutant GISTs. PD-L1 expression was negatively associated with tumor size. The immunotherapy targeting PD-1/PD-L1 checkpoint and IDO may be valuable.

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Data Availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

IDO:

Indoleamine-2,3-dioxygenase

PD-1:

Programmed cell death protein-1

PD-L1:

Programmed cell death protein ligand-1

GISTs:

Gastrointestinal stromal tumors

PDGFRA:

Platelet-derived growth factor receptor alpha

TKIs:

Tyrosine kinase inhibitors

NIH:

National Institutes of Health

TIL:

Tumor-infiltrating lymphocyte

Treg:

Regulatory T cell

TMA:

Tissue microarray

TPS:

Tumor proportion score

NCCN:

National comprehensive cancer network

NSCLC:

Non-small cell lung cancer

HPF:

High-power field

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Funding

This study was supported by the National Natural Science Foundation of China (81773080).

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Author notes

  1. Xiangfei Sun, Jianyi Sun, and Wei Yuan contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China

    Xiangfei Sun, Jianyi Sun, Xiaodong Gao, Min Fu, Anwei Xue, He Li, Ping Shu, Yong Fang, Kuntang Shen, Yihong Sun, Jing Qin & Xinyu Qin

  2. Department of Pathology, Zhongshan Hospital, Fudan University School of Medicine, #180 Fenglin Road, Shanghai, 200032, China

    Wei Yuan & Yingyong Hou

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  1. Xiangfei Sun
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Contributions

X.S., J.S., and W.Y. designed the work and wrote the manuscript. X.G., M.F., A.X., H.L., P.S., and Y.F. analyzed and interpreted the patient data. W.Y. and Y.H. performed the immunohistochemistry examinations. Y.H., K.S., J.S., J.Q., and X.Q. revised the manuscript. X.S., J.S., and W.Y. were major contributors in writing the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yingyong Hou or Kuntang Shen.

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The authors declare that they have no conflict of interest.

Ethical Approval

This study was approved by the Clinical Research Ethics Committee of Zhongshan Hospital, Fudan University.

Informed Consent

Informed consent was acquired from all patients for the acquisition of clinical and pathological information and the use of surgical specimens.

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Sun, X., Sun, J., Yuan, W. et al. Immune Cell Infiltration and the Expression of PD-1 and PD-L1 in Primary PDGFRA-Mutant Gastrointestinal Stromal Tumors. J Gastrointest Surg 25, 2091–2100 (2021). https://doi.org/10.1007/s11605-020-04860-8

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